This invention relates to magnetic resonance imaging complexes and more particularly to methods for reducing the toxicity thereof.
It has been found that physiologically well-tolerated complex salts formed from the anion of a complexing acid (ligand) and one or more central ions of an element with an atomic number of 21 to 29, 42, 44 or 57 to 83 (paramagnetic metal) and, optionally, also formed from one or more Physiologically biocompatible cations of an inorganic and/or organic base or amino acid, are suitable for producing diagnostic media for use in magnetic resonance imaging or X-ray diagnosis. We have referred to these materials as paramagnetic metal chelates. U.S. Pat. No. 4,647,447 describes the use and the manufacture of paramagnetic metal chelates in detail.
However, it has been found that these paramagnetic chelates employed in magnetic resonance imaging acutely reflect more toxicity when injected in high concentration or at rapid rates. Generally, this toxicity has been manifested as strong convulsions.
Believing this toxicity to stem from the absorption of free paramagnetic metals in the blood, it has been the previous practice to reduce such toxicity by formulating with an additive of excess ligand such as EDTA as its sodium and/or calcium salts. These additives were employed as scavengers for the paramagnetic metal in the manner disclosed by Bernard Osler et al. in Toxicology and Applied Pharmacology. Volume 5. Pages 142-162 published in 1963 under title of "Safety Evaluation Studies of Calcium EDTA".
However, a method for reducing such toxicity without the need for employing excess ligand and without having to correlate the amount of excess ligand to the projected amount of free metal in the blood would be a substantial advancement in the art.